This project continues our examination of the reulation of uptake, storage, and release of serotonin and other biogenic amines in human platelets. Plasma-membrane uptake of serotonin is affected little by metabolic poisons or by the presence of cytoplasmic serotonin, but is inhibited completely during cellular secretion. Although vesicular uptake of serotonin may be associated with proton gradients, plasma-membrane uptake of serotonin does not appear to proceed by a similar mechanism. Vesicular nucleotides are quite restricted in motion in intact cells, possibly due to binding with vesicular calcium. Since total vesicular calcium and phosphorus do not change following large alterations in serotonin content, it seems unlikely that all three substances are stored as micellar complex. Platelets appear to be capable of a graded secretory response, rather than an all-or-none type of secretion, which may be determined in part by the frequency with which each cell has been stimulated while in the circulation. BIBLIOGRAPHIC REFERENCES: Costa, J.L., Murphy, D.L., and Kafka, M.S.: Demonstration and evaluation of apparent cytoplasmic and vesicular serotonin compartments in human platelets. Biochem. Pharmacol., 26: 517-521, 1977. Costa, J.L., Detwiler, T.C., Feinman, R.D., Murphy, D.L., Patlak, C.S., and Pettigrew, K.D.: Quantitative evaluation of the loss of human-platelet dense bodies following stimulation by thrombin or A23187. J. Physiol. 264: 297-306, 1977.